CircularRNA as novel biomarkers in liver diseases

Abstract

The liver is an essential organ that is primarily responsible for digestion and eliminating toxic substances from the body. After the industrial revolution, Western diet and lifestyle changes have increased the incidence of several liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). NAFLD and NASH are mostly asymptomatic at early stages, and the disease progression from NAFLD to life-threatening HCC remains not fully understood. Circular RNA (circRNA) is consist of a circular structure, and the circRNA-microRNA(miRNA)-mRNA axes have been shown to be involved in several cellular events, including apoptosis, vascularization, metastasis, etc. The highly stable structure of circRNAs has enabled themselves to be used as putative biomarkers of several diseases. Here, we conducted a literature review and discussed the identified roles of circRNAs in NAFLD, NASH, liver cirrhosis, and HCC. For example, deficiency of circRNA_0046366 and circRNA_0046367 has been shown as the characteristics of NAFLD, and restoration of these circRNAs ameliorates the oxidative stress, lipotoxicity, and disease severity in NAFLD. Silencing of circ_0071410 was shown to alleviate hepatic stellate activation, the key step of liver cirrhosis. CDR1 and circ_0067934 can facilitate the invasion and metastasis of HCC, while circMTO1 negatively regulates the progression of HCC. Although several research works have been conducted, the whole picture of circRNA-related underlying mechanisms is unclear. Future works using high-throughput bioinformatic approaches will be needed to delineate the role of circRNAs in liver diseases and to further develop novel diagnostics and therapeutics.

<p>Hsa_circ_0006916 Knockdown Represses the Development of Hepatocellular Carcinoma via Modulating miR-599/SRSF2 Axis</p>

“…29 CircRNAs are implicated in the progression of liver diseases including HCC via regulating various cell events. 30 A previous study suggested that circ_0006916 played an important role in HCC development. 15 In this study, we found that circ_0006916 could repress HCC development.…”

Role of ncRNAs in modulation of liver fibrosis by extracellular vesicles

“…It is a unique type of single-stranded lncRNA arranged in a closed loop structure, which is highly stable and resistant from RNA degrading enzymes [80,81]. In recent years, increased research has focused on the role of circRNAs as ceRNA or miRNA sponges, revealing their strong association with the development of various diseases and their possible use as diagnostic biomarkers [82][83][84]. The first report indicating an involvement of circRNAs in liver fibrosis comes from Chen and colleagues [85], who indentified differentially expressed circRNAs associated with HSC activation.…”

Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases

“…A certain number of circRNAs have been discovered as potential biomarkers or therapeutic targets for HCC [36][37][38][39][40][41][42][43]. As well as for HCC, circRNAs play an important role in non-neoplastic chronic liver diseases, such as ALD, MAFLD, liver fibrosis, and autoimmune diseases through epigenetic mechanisms [11,12,[44][45][46].…”